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The impressive efficacy of imatinib in CML is well-established and is correlated directly with transcription levels of its target, bcr-abl. Higher doses of imatinib are indicated in pts with rising levels of bcr/abl transcripts. RQ-PCR is considered to be the optimal method for determining levels of bcr/abl transcripts in pts with CML. Furthermore, the degree of reduction of total leukemia cell mass by imatinib as measured by FISH and RQ-PCR correlates with progression-free survival. This study was undertaken to determine the potential of RQ-PCR to predict ongoing pt response to imatinib based on the duration of complete cytogenetic remission (CCyR).

Materials and Methods

Prospective, multicentric study initiated in November 2005

A total of 177 pts were enrolled, 164 from Argentina, 13 fron Uruguay

Of these, 154 pts with CP-CML presently in CCyR and treated with 400 mg/d imatinib were included.

Pts were divided into two groups based on their 1st line treatments :

IFN/Cytarabine, 83 pts (51%)

Imatinib, 77 pts (49%)

At baseline, all pts were studied by both FISH and RQ-PCR

Follow up RQ-PCR was then performed at 6, 12, and 18 months

Imatinib median duration was 26 months (range 6-64)

All pts (100%) completed the first and second evaluations, whereas only 37% had their third evaluation as of March 2007.

Overall, 78% of pts who were FISH (-) had improved or maintained MR on Imatinib therapy at 12 months of follow up.

The MRs did not vary significantly based on Sokol risk group classification.

All pts are presently still in hematologic remission.

Clinical/Scientific Implications

This study presents data that provide a very nice correlation between clinical, molecular, and cytogenetic parameters in the treatment of chrnic-phase CML with the novel bcr-abl targeting agent, Imatininb. In the study population reported here, an overall 78% of pts who were FISH (-) had improved or maintained MR on Imatinib therapy at 12 months of follow up. Furthermore, all pts reported here continue to be in complete remission, both cytogenetically and hematologically. Thus it appears that RQ-PCR is indeed a useful indicator of ongoing response to long-term Imatinib therapy in chronic phase CML pts. In this era of long-term Imatinib treatment, additional studies are warranted to evaluate the identification and characterization of patients destined to be late-progressors, as well as to better understand the longer-term adverse effects profile of imatinib in this population.

Dec 7, 2010 - Nilotinib may improve survival in some chronic myeloid leukemia (CML) patients, and patients with various types of CML respond well to ponatinib, according to research being presented at the annual meeting of the American Society of Hematology, held from Dec. 4 to 7 in Orlando, Fla. Other studies being presented outline the optimal use of imatinib, address how a new gene target functions for several myeloid malignancies, highlight a tool for predicting acute myeloid leukemia outcomes, and address the use of mitoxantrone in acute lymphoblastic leukemia.